In the last years there has been accumulating evidence that physical inactivity may accelerate the aging processes. Moreover, a genetic substrate that modulates the aging rate has been suspected in recent literature. However, it is possible that some genetic substrates actually act in an indirect way, modulating the levels of spontaneous physical activity. Therefore the present work investigates (i) the genetic determinants of spontaneous physical activity and (ii) using an experimental approach, the effects of physical activity on cognitive impairment have been addressed. Given the great complexity of the study of genetic determinants in humans, we have taken advantage of the technology introduction of transgenic animals. Specifically, through a meta-analysis approach, the brain distribution of genes that are involved in the change of locomotor activity has been investigated. To this aim, about 50000 abstracts and papers in extenso concerning behavioral studies in knockout mice have been analyzed; data have been collected in a database and crossed to two databases, the Allen Brain Atlas and the Sym Atlas, to verify the brain distribution of genes deleted. Results show that the genes accompanied, after deletion, by an increase of locomotor activity are expressed at higher levels in all brain regions compared to those that after deletion cause locomotor hypoactivity. Therefore, we investigated how the levels of spontaneous physical activity are distributed in an aged population. To this aim, 438 subjects (age 50-86 years) have been characterized for their motor ability (AAPHERD battery), their spontaneous physical activity (test PASE) and their cognitive status (tests MMSE, FAB, attentional matrix). Moreover subjects have been randomized in two experimental groups, the first one fulfilling an intense aerobic and potentiation physical training protocol, and a second one with a light aerobic training. The training, three times per week, one hour per session, lasted for one year. After six months and one year subjects have been tested again using the above battery of tests. Results at six months show that spontaneous physical activity has a bimodal distribution in male aged population. Noteworthy, strong differences have been noted between the groups of more active aged subjects compared to the less active ones: the first takes less drugs and has better scores in agility tests and in attentional tests. To verify the causal relationship between physical activity and these variables, we compared the scores before and after the physical training. Results confirm that physical activity decrease the number of drugs and improves motor abilities. However, attentional scores do not improve after this specific physical training. In conclusion, murine models suggest a genetic substrate for differences in physical activity in the population; data from the aged population suggest that levels of spontaneous physical activity, caused by, at least in part, genetic substrates, could cause the decrease of physical abilities and the increase in the number of drugs taken during ageing process.
Relazione fra attività fisica, modifiche dell'umore ed invecchiamento: aspetti genetici e preventivi
MIGNOGNA, Pasquale
2012-05-04
Abstract
In the last years there has been accumulating evidence that physical inactivity may accelerate the aging processes. Moreover, a genetic substrate that modulates the aging rate has been suspected in recent literature. However, it is possible that some genetic substrates actually act in an indirect way, modulating the levels of spontaneous physical activity. Therefore the present work investigates (i) the genetic determinants of spontaneous physical activity and (ii) using an experimental approach, the effects of physical activity on cognitive impairment have been addressed. Given the great complexity of the study of genetic determinants in humans, we have taken advantage of the technology introduction of transgenic animals. Specifically, through a meta-analysis approach, the brain distribution of genes that are involved in the change of locomotor activity has been investigated. To this aim, about 50000 abstracts and papers in extenso concerning behavioral studies in knockout mice have been analyzed; data have been collected in a database and crossed to two databases, the Allen Brain Atlas and the Sym Atlas, to verify the brain distribution of genes deleted. Results show that the genes accompanied, after deletion, by an increase of locomotor activity are expressed at higher levels in all brain regions compared to those that after deletion cause locomotor hypoactivity. Therefore, we investigated how the levels of spontaneous physical activity are distributed in an aged population. To this aim, 438 subjects (age 50-86 years) have been characterized for their motor ability (AAPHERD battery), their spontaneous physical activity (test PASE) and their cognitive status (tests MMSE, FAB, attentional matrix). Moreover subjects have been randomized in two experimental groups, the first one fulfilling an intense aerobic and potentiation physical training protocol, and a second one with a light aerobic training. The training, three times per week, one hour per session, lasted for one year. After six months and one year subjects have been tested again using the above battery of tests. Results at six months show that spontaneous physical activity has a bimodal distribution in male aged population. Noteworthy, strong differences have been noted between the groups of more active aged subjects compared to the less active ones: the first takes less drugs and has better scores in agility tests and in attentional tests. To verify the causal relationship between physical activity and these variables, we compared the scores before and after the physical training. Results confirm that physical activity decrease the number of drugs and improves motor abilities. However, attentional scores do not improve after this specific physical training. In conclusion, murine models suggest a genetic substrate for differences in physical activity in the population; data from the aged population suggest that levels of spontaneous physical activity, caused by, at least in part, genetic substrates, could cause the decrease of physical abilities and the increase in the number of drugs taken during ageing process.File | Dimensione | Formato | |
---|---|---|---|
Tesi_P_Mignogna.pdf
accesso aperto
Tipologia:
Tesi di dottorato
Dimensione
1.05 MB
Formato
Adobe PDF
|
1.05 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.